Interleukin-17-producing T cell (Th17) is an important T-helper subset characterized by a unique transcriptional program regulated through activation of STAT3 pathways by IL-6, IL-21 and IL-23 (10-12). Although much is known about the role of STAT3 in regulating differentiation of Th17 cells and their role in Th17-mediated autoimmune diseases, its function in other lymphocyte subsets is not well understood. In this study, we have investigated: (i) mechanisms that may explain the frequent involvement of STAT3 and Th17 cells in the etiology of organ-specific autoimmune diseases, such as uveitis and multiple sclerosis; (ii) Whether STAT3 has effects on the proliferation, survival or effector functions of other T cell subsets. We used a combination of genomic and genetic tools to provide the first evidence that STAT3 binds directly to the miR-155 locus and that STAT3 is required for miR-155 expression. Furthermore, Using miR155 mice and mice with targeted deletion of STAT3 in CD4+ T cells we showed that STAT3 activates miR-155 in Th17 cells and acts in concert to promote experimental autoimmune uveitis (EAU), an animal model of human uveitis. We further showed that STAT3-dependent increase in miR-155 expression in vivo correlated temporally with onset of EAU and miR-155-/- or CD4-STAT3KO mice did not develop EAU. We also generated mice with Socs3 deletion in CD4 T cell compartment (CD4-SOCS3KO) to determine in vivo effects of the loss of Socs3 in the T cell-mediated autoimmune disease, EAU. We show that CD4-SOCS3KO mice were protected from acute and chronic uveitis. Protection from EAU correlated with enhanced expression of CTLA4 and expansion of IL-10 producing Tregs with augmented suppressive activities. We further showed that SOCS3 interacts with CTLA4 and negatively regulates CTLA4 levels in T cells, providing mechanistic explanation for the expansion of Tregs in CD4-SOCS3 during EAU.